Recently, a method to measure free insulin-like growth factor-I (IGF-I) levels has been developed. Free IGF-I levels may have greater physiological and clinical relevance than total (bound and free) IGF-I. The associations between the circulating IGF-I/IGF binding protein (IGFBP) system and cardiovascular disorders was studied. In a cross-sectional study of 218 healthy persons (103 men, 115 women) aged 55 to 80 years, fasting serum (total and free) IGF-I and IGFBP-1 levels, lipid profile, insulin, and glucose were measured. In addition, blood pressure, body mass index (BMI), and waist-hip ratio (WHR) were measured. Ultrasonography of both carotid arteries was performed to investigate the presence of atherosclerotic lesions. A history of angina pectoris, the presence of a possible or definite myocardial infarction on the ECG, and plaques in the carotid arteries were used as indicators of presence of cardiovascular signs and symptoms. Free IGF-I was inversely related to serum triglycerides (P=.04, adjusted for age and sex). Mean free IGF-I levels in subjects without signs or symptoms of cardiovascular diseases were significantly higher than in those with at least one cardiovascular symptom or sign (P=.002, adjusted for age and sex). Free IGF-I levels were also higher in subjects who had no atherosclerotic plaques in the carotid arteries (P=.02, adjusted for age and sex) and who had never smoked (P=.02, adjusted for age and sex). IGFBP-1 showed an inverse relation with insulin, BMI, and WHR and a positive relation with HDL cholesterol. The associations between IGFBP-1 levels and HDL cholesterol, WHR, and BMI remained significant after adjustment for fasting insulin levels. High fasting serum free IGF-I levels are associated with a decreased presence of atherosclerotic plaques and coronary artery disease and lower serum triglycerides, whereas high fasting IGFBP-1 levels are associated with a more favorable cardiovascular risk profile. The findings suggest that the IGF-I/IGFBP system is related to cardiovascular risk factors and atherosclerosis.